Conclusions: Although HIV infection is characterized by a long period of clinical latency, HIV actively replicates in the lymphoid organs during this period, despite the fact that virus replication is barely detectable or absent in peripheral blood. Histopathologic alterations (ie, follicular hyperplasia and expansion of the FDC network) may partly explain the dichotomy between the levels of viral burden in the lymphoid organs versus peripheral blood. These findings demonstrate that lymphoid organs function as reservoirs and potentially as major sites of virus replication. However, they also indicate that the peripheral blood does not accurately reflect the actual state of HIV disease, particularly in early-stage infection. In fact, HIV disease is active and progressive even when there is little evidence of disease activity in peripheral blood. Therefore, a state of true microbiological latency is non-existent during the course of HIV infection.